Acute Myelogenous Leukemia
Conditions
Keywords
Phase I, Phase II, acute myelogenous leukemia, AML, cancer
Brief summary
The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD4877 based on the side effects experienced by patients that receive AZD4877 on a daily times 3 schedule in acute myelogenous leukemia (AML). For enrollment information see the Central Contact information below
Interventions
DRUGAZD4877
intravenous infusion administered on days 1, 2 and 3
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Part A: Relapsed or refractory leukemia for which no standard therapies are anticipated to result in a durable remission * Part B: AML who have had no more than two prior relapses or failed to achieve remission after at least one induction treatment. * Patients with prior allogeneic transplants who remain clinically stable for ≥2 weeks or more off immunosuppressive therapy
Exclusion criteria
* Promyelocytic acute myelogenous leukemia * Prior allogeneic transplant requiring immunosuppressive therapy or treating physician does not consider patient to be a candidate for allogeneic transplantation. * Liver injury
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs) | Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period. | To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs) |
| To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR) | Response is evaluated after a maximum of 2 courses of induction therapy. | Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure. |
| To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ] | PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8. | Maximum plasma concentration, Cmax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR) | Response is evaluated after a maximum of 2 courses of induction therapy. | Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure. |
| To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs | Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible. | — |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were recruited at 4 study sites in the United States and 1 study site in Canada between July 2007 and February 2009 \[Part A\] and between March 2009 and July 2009 \[Part B\].
Pre-assignment details
Following enrolment there was screening period of up to 28 days, after which if all inclusion/exclusion criteria were met, patients were dosed with AZD4877
Participants by arm
| Arm | Count |
|---|---|
| AZD4877 AZD4877 \[ Time Frame: administered on days 1,2 and 3\] | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 8 |
Baseline characteristics
| Characteristic | AZD4877 |
|---|---|
| Age, Customized >=18 - < 65 Years | 6 Participants |
| Age, Customized < 18 Years | 0 Participants |
| Age, Customized >=65 - < 75 Yrs | 1 Participants |
| Age, Customized >=75 Yrs | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized White | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
Primary
To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Time frame: Response is evaluated after a maximum of 2 courses of induction therapy.
Population: 8 of 9 patients in Part B were evaluable for response following a maximum of 2 courses of induction therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD4877 | To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR) | 0 Participants |
Primary
To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]
Maximum plasma concentration, Cmax
Time frame: PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8.
Primary
To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)
To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
Time frame: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.
Secondary
To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR)
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Time frame: Response is evaluated after a maximum of 2 courses of induction therapy.
Secondary
To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs
Time frame: Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible.